title: Thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine suicide gene therapy-induced cell apoptosis in breast cancer cells.
abstract: The present study was conducted to explore the efficacy of suicide gene therapy with thymidine kinase (TK) in combination with cytosine deaminase (CD) for breast cancer. The expression of CD/TK was detected in the infected cells by RT-PCR. The killing effect on MCF-7 cells following treatment was analyzed by MTT assay. The morphological characteristics of the cells were observed by electron microscopy, and the distribution of the cell cycle was analyzed by flow cytometry. Caspase‑3 and -8 activities were detected by absorption spectrometry. Cytotoxic assays showed that cells transfected with CD/TK became more sensitive to the prodrugs. Morphological features characteristic of apoptosis were noted in the MCF‑7 cells via electron microscopy. The experimental data showed that the proportion of MCF-7 cells during the different phases of the cell cycle varied significantly following treatment with the prodrugs. The activity of caspase‑3 gradually increased following treatment with increasing concentrations of the prodrugs. We conclude that the TK/ganciclovir and CD/5-fluorocytosine suicide gene system used here induces apoptosis in breast cancer cells, and provides a promising treatment modality for breast cancer.
authors.affiliation: Department of General Surgery, Nan Shan District People's Hospital, Shenzhen, Guangdong 518052, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Kong
authors.forename: L
authors.initials: L
authors.lastname: Tao
authors.forename: K
authors.initials: K
authors.lastname: Qi
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000963:Antimetabolites / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D043525:Cytosine Deaminase / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005437:Flucytosine / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D061986:MCF-7 Cells; D046529:Microscopy, Electron, Transmission; D011355:Prodrugs; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000963:Antimetabolites; D000998:Antiviral Agents; D011355:Prodrugs; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005437:Flucytosine; D013937:Thymidine Kinase; D020169:Caspases; D043525:Cytosine Deaminase; D015774:Ganciclovir